The objective of this proposal is to examine the hypothesis that sudden infant death syndrome (SIDS) results from apnea in an infant with reduced central respiratory drive and triggered by stimulation of the laryngeal inhibitory reflex. We have recently shown in piglets that bathing the laryngeal region with water or cow's milk often produces sustained apnea leading to asphyxial death of the animal. This sequence could be interrupted by flushing the laryngeal area with normal saline, by cutting the superior laryngeal nerves, or by anesthetizing the laryngeal epithelium with xylocaine. However, approximately half the animals manifested transitory respiratory inhibition followed by recovery. This suggests important differences in central respiratory drive. This concept was supported by subsequent evidence that depression of central respiratory drive by chemical means using chloralose markedly enhanced laryngeal reflex inhibition of respiration. In the course of these studies it was observed that anemic piglets were more than twice as sensitive to chloralose depression of central respiratory drive. The proposed studies have been designed to examine the consequences of chronic anemia and acute hemodilutional anemia as a potential physiological mechanism for reduced central respiratory drive and increased vulnerability to sustained apnea triggered by the laryngeal chemoreceptor reflex. The models for chronic anemia will include iron deficiency anemia, and hemolytic anemia produced with acetylphenylhydrazine. Peripheral chemoreceptor function will also be examined in the chronically anemic animals. Physiologic data will be compared with structural changes in the nervous system at the level of the medulla in the developing piglet with chronic anemia. These studies will be extended to the unanesthetized but tranquilized piglet model. The observation that mean hematocrit values in infants are lowest at a time when the frequency of SIDS is highest (2-4 months) and that these infants often have backgrounds which are associated with a high incidence of anemias is consistent with the hypothesis to be explored.